Net Clinical Benefit of Edoxaban for Stroke, Mortality, and Bleeding Risk : Modeling Projections for a European Population

ObjectivesThe purpose of this study was to determine, in a model based on Europeans at risk of stroke by virtue of atrial fibrillation (AF), the net clinical benefit of edoxaban in the reduction of the risk of stroke, mortality, and of hemorrhage.BackgroundVitamin K antagonists (e.g., warfarin) are commonly underused because of such factors as fear of hemorrhage in patients with high-risk AF. The non–vitamin K antagonist oral anticoagulants are similarly or more effective than warfarin and have lower rates of serious hemorrhage. Although outcomes of the ENGAGE AF-TIMI 48 trial that compared the non–vitamin K antagonist oral anticoagulant edoxaban with warfarin and indicated similar efficacy and better safety compared with warfarin for stroke prevention in AF, the application of trial data to the general population is unknown.MethodsThis study modelled a treatment effect of edoxaban on the risks of thromboembolism, major bleeding, and death in a real-world population of patients with AF drawn from the Euro Heart Survey, and extrapolated this to the general European population.ResultsIn those at high risk of stroke (CHA2DS2VASc ≥2), edoxaban would need to be taken by 319 patients to prevent 1 thromboembolism, major bleeding event, or death compared with warfarin, and by 41 patients to prevent 1 thromboembolism or death compared with no treatment. These translate to demonstrating a net clinical benefit of 8.9 events saved per 1,000 patients with edoxaban 60 mg. Modeling these data to the population of Europe of 508 million, use of edoxaban 30 mg and 60 mg instead of warfarin would, respectively, prevent approximately 19,400 and 30,300 thromboembolic events, major bleeds, and deaths annually.ConclusionsOur modeling exercise suggests that the use of edoxaban for thromboprophylaxis in AF based on current guidelines could provide a profound benefit on rates of stroke, major bleeds, and deaths in European patients with AF.